The aim of the research is to understand how cell-cell interactions regulate the formation of a critical cell type in the developing retina. Cell-cell interactions mediated by extracellular factors play a major role in the determination of cell type during development. They are the main factor in cell determination in both vertebrate and Drosophila retina. Drosophila can be studied by identifying genes through mutations that affect development, and characterizing how the genes function through developmental and molecular studies. Therefore the determination of R8 photoreceptor cells in Drosophila retina will be studied as a model to understand mechanisms of cell-cell interaction. In this system the behavior of individual calls can be studied, genetic techniques used" to identify and study gene products that are involved. R8 photoreceptor cells are the first cells to differentiate in the retina. The pattern of R8 photoreceptor cells is determined by a process involving lateral inhibition. Determination of cells in other parts of the Drosophila nervous system appears to be similar and requires some of the same genes. Lateral inhibition is also used to determine various cell types in other organisms. Two mutations known to affect the pattern of R8 photoreceptor cells are scabrous and Notch. scabrous encodes a putative secreted protein. Notch encodes a transmembrane protein. Notch is the Drosophila homologue of TAN-1 , a human proto-oncogene. scabrous and Notch also regulate cell determination in other parts of the Drosophila nervous system. To study cell-cell interactions in R8 photoreceptor determination, further important genes will be identified using a novel genetic screen based on properties of scabrous and Notch mutations. The roles of previously known genes will be investigated using scabrous expression as a sensitive assay for determination in their mutants. To test if Notch or other proteins is a receptor for scabrous, the nature of the scabrous protein products and Notch scabrous binding will be investigated biochemically.